MDA5 (show IFIH1 Proteins) and LGP2 act as independent positive regulators of the IFN response in fish. the LGP2 variant with a deletion of 54 amino acids at the C terminus acts as a negative regulator for LGP2-elicited antiviral signaling.

This review briefly summarizes the RLR system, and focuses on the relationship between LGP2 and MDA5 (show IFIH1 Proteins), describing in detail how these two proteins work together to detect foreign RNA and generate a fully functional antiviral response.

L region antisense RNA of EMCV is a key determinant of innate immunity to the virus and represents an RNA that activates LGP2 associated MDA5 (show IFIH1 Proteins) in virally-infected cells.

Experiments with paramyxovirus V protein-insensitive proteins revealed that the primary outcome of LGP2 interference is suppression of its ability to synergize with MDA5 (show IFIH1 Proteins).

Data show that LGP2 is able to synergize with melanoma differentiation associated gene-5 (mda-5 (show IFIH1 Proteins)) to render cells to induction by poly(I:C), but did not enhance retinoic acid-inducible gene-I (RIG-I (show DDX58 Proteins)) to induce type I interferon (show IFNA Proteins) in response to poly(I:C).

results demonstrate previously unrecognized properties of LGP2 ATP hydrolysis and RNA interaction and provide a mechanistic basis for a positive regulatory role for LGP2 in antiviral signaling

findings demonstrate a regulatory role for LGP2 in the response to cytosolic DNA, an intracellular bacterial pathogen, and a DNA virus, and provide a plausible mechanistic hypothesis as the basis for this activity

data suggest that LGP2 facilitates viral RNA recognition by RIG-I and MDA5 through its ATPase domain.

DHX58 Protein Profile

Protein Summary

Acts as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1- dependent signaling events. Can have both negative and positive regulatory functions related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on DDX58/RIG-I DDX58/RIG-I for binding to the viral RNA, binding to DDX58/RIG-I and inhibiting its dimerization and interaction with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1 thereby inhibiting activation of interferon regulatory factor 3 (IRF3). Its positive regulatory role may involve unwinding or stripping nucleoproteins of viral RNA thereby facilitating their recognition by DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune response to various RNA viruses and some DNA viruses such as poxviruses, and also to the bacterial pathogen Listeria monocytogenes. Can bind both ssRNA and dsRNA, with a higher affinity for dsRNA. Shows a preference to 5'-triphosphorylated RNA, although it can recognize RNA lacking a 5'-triphosphate.